Project Summary Kidney stones are common and costly. They are associated with severe pain, and increased rates of chronic kidney disease, hypertension, and coronary heart disease. Despite this importance, there is much that is not known about stone risk factors and preventative options are limited. We propose to study two novel factors, circadian rhythm disruption and bisphosphonate medications, and the association with kidney stone formation within the Nurses? Health Study II cohort. Disruptions in circadian rhythm, as in night shift work, may be a modifiable risk factor for kidney stones because of the known diurnal variation in kidney function and kidney stone risk, association between a melatonin receptor and recurrent kidney stones, and the possible lowering effect of melatonin on urinary calcium. Higher urinary calcium levels are associated with increased risk of kidney stones. Bisphosphonate medications may also reduce urinary calcium; if they also reduce kidney stone risk, this could be a new preventative option for patients with calcium-containing kidney stones. In Aim 1, we will examine the association between shift work and kidney stone formation. We hypothesize that night shift work will be associated with higher risk of kidney stone formation. In Aim 2, we will study bisphosphonate use and risk of kidney stones. We will also do a cross-sectional analysis using urine samples to compare mean urinary calcium levels between participants using and not using bisphosphonates. We hypothesize that bisphosphonate use will be associated with lower risk of kidney stone formation and lower mean urinary calcium excretion. Characterizing additional risk factors and identifying novel treatments will contribute to understanding of kidney stone formation and provide additional preventative strategies for patients and providers.